Field of the Invention
The present invention relates to the field of micro magnetic mechanical systems of micro-cantilevers type, for force measurements and manipulation of small objects such as micro sized beads and macromolecules DNA
Description of the Related Art
During diverse molecular processes forces are generated inside cells such as transcription or replication of DNA, protein unfolding, translocation of proteins across membranes, and cell locomotion. At present, due to their versatility, atomic force microscopy, and optical and magnetic tweezers are the most commonly used techniques to measure force at the single molecule level. Optical trapping allows for the application of forces and the manipulation of biomolecules such as DNAs, and the detection of folding and unfolding events of proteins at a single molecule level. In addition to forces, magnetic tweezers apply torques on micro-magnetic beads linked to single molecules through the displacement and rotation of the external magnets. An advantage of this methodology is that it generates very stable force fields that can be simultaneously applied to many individual molecules within the field of view of the microscope. Of the aforementioned techniques, a disadvantage of magnetic tweezers is that they have the lowest spatial resolution (5-10 nm), but they are suitable for use with very low forces (≈0.1 pN) and do not cause radiation heating or photo damage to the sample. Conversely, micro cantilevers have important advantages with respect to magnetic and optical tweezers since they can be manufactured in a broad range of sensing forces and a variety of systems are available to detect their deflections, which provides high accuracy force assessment over a wide dynamic range. However, micro cantilevers have two important disadvantages for the mechanical assessment of single molecules; firstly, the cantilever tip requires a specific surface functionalization in order to ensure an appropriate and selective linkage to a particular molecule, and secondly, following contact with the tip-molecules, several trials and elaborated procedures may be required to ensure that only one single molecule has been linked to the cantilever. In addition, once a molecule has been tested, testing another molecule from the sample (with the same cantilever) requires the breaking of the link in order to create a new link, which increases the uncertainty of the operation of subsequent links. This is a serious limitation when a high number of individual molecules are tested and statistical analysis is required, or when the same molecule has to be tested in a non-destructive manner.